Overview of Bacterial STDs: Gonorrhea,
Chlamydia and Syphilis
Burning questions
Jeffrey D. Klausner, MD, MPH
Professor of Medicine and Public Health
Attending Physician Ronald Reagan Medical Center
Division of Infectious Diseases: Global Health
David Geffen School of Medicine
Department of Epidemiology
Karin and Jonathan Fielding School of Public Health
Today’s talk
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Gonorrhea
Chlamydia
Syphilis
Trichomoniasis
Herpes
HPV
Not covering HIV, hepatitis B, other
Case
• 28 year old man
with urethral
discharge
3
Differential diagnosis of urethritis
• Infectious
Neisseria gonorrhoeae
Chlamydia trachomatis
Mycoplasma genitalium
Trichomonas vaginalis
Herpes simplex virus 1 and 2
Oral flora---streptococci, anaerobes, haemophilus species
• Non-infectious
Trauma--physical or chemical (drugs), post-catheterization
or sex-play related
Autoimmune—Reactive arthritis/ conjunctivitis syndrome
Uncomplicated gonococcal infection
Gram-negative
intracellular diplococci
Gram stain of urethral discharge
1000x
Neisseria gonorrhoeae
Urethra
Cervix
Pharynx
Rectum
Detection of N. gonorrhoeae infection
Sensitivity
Specificity
Gram stain
92%
90%
Culture
95%
100%
DNA/RNA amplification*
95%
99%
*May be used on clinician or self-collected vaginal, cervical,
rectal, pharyngeal specimens and urine
Gonorrhea—Rates, United States, 1941–2013
2012-Fig 11. SR, Pg 19
Gonorrhea—Rates by County
United States 2013
2012-Fig 20. SR, Pg 21
Gonorrhea—Rates by Age and Sex
United States, 2013
2012-Fig 21. SR, Pg 21
Gonorrhea—Rates by Race/Ethnicity
United States, 2008–2013
†NHOPI
= Native Hawaiian and Other Pacific Islanders.
NOTE: Includes 38 states and the District of Columbia reporting race/ethnicity data in Office of Management and
Budget compliant formats during 2008–2012.
2012-Fig 19. SR, Pg 23
Percentage of Isolates in Which Minimal Inhibitory Concentrations (MICs) of Cefixime Were 0.25 μg/mL or Higher, 2005–2011
Bolan GA et al. N Engl J Med; Feb., 2012
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Percentage of Neisseria gonorrhoeae Isolates with Ceftriaxone
Minimum Inhibitory Concentrations (≥0.125 μg/ml),
Gonococcal Isolate Surveillance Project (GISP), 2005 – 2013
2012-Fig 24. SR, Pg 25
Multi-drug treatment for gonorrhea
Ceftriaxone 250 mg IM once AND
azithromycin 1 gm PO once or
doxycycline 100 mg PO twice daily x 7 days
Plus partner treatment
Retesting at 3 months
13
MMWR CDC STD Treatment Guidelines Update, August 2012
Penicillin, Tetracycline, and Ciprofloxacin Resistance Among
Neisseria gonorrhoeae Isolates, 2013
Any QRNG “Cipro-R” = 16.1%
NOTE: PenR = penicillinase producing Neisseria gonorrhoeae and chromosomally mediated penicillinresistant N. gonorrhoeae; TetR = chromosomally and plasmid mediated tetracycline-resistant N.
gonorrhoeae; and QRNG = quinolone-resistant N. gonorrhoeae.
2012-Fig 27. SR, Pg 27
Fluoroquinolone resistance in
Neisseria gonorrhoeae
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Real-time PCR Melting Curves: FRET probe binding to
gyrA at serine 91 detects wild-type vs. altered gene
“Hyb Probes”: using Fluorescence Resonance
Energy Transfer (FRET)
Detector Probes,
No PCR product to detect
PCR product,
To be detected
Can detect base-pair mutations
16
Siedner et al, JCM, 2007; Siedner et al, Int J STD AIDS, 2008
Molecular-based resistance testing
• Rapid detection of NG
• Subsequent detection of key
antimicrobial resistance
elements
• Enable targeted treatment
• Reduce antibiotic selection
pressure
• Decrease emergence of
resistance
NIH R21AI109005
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Case
19 year old female used SexInfo text message service
(Text “SexInfo” to 61827) and comes in for a check-up.
She has one regular partner for 6 months and has no
symptoms.
What STD screening tests are appropriate?
Recommended STI screening in
sexually active female < 25 years
• Chlamydia trachomatis/ Neisseria gonorrhoeae, annually
• HIV test, once
Consider
Herpes simplex virus type 2 antibody
Avoid
PAP smear (only if sexually active > 3 years)
USPSTF, 2013
Screening tests for chlamydial infection
• Nucleic acid amplification tests
– DNA amplification (Roche, Bayer, Abbott, BD, Cepheid)
– RNA amplification (Hologic Gen-Probe)
Cervicitis
Mucopurulent discharge
STD Atlas, Mosby: 1997
Friability
Slide courtesy of M. Leibowitz
Chlamydia—Rates by County, United States
2013
2011-Fig 4. SR, Pg 10
Chlamydia—Rates by Age and Sex, United
States, 2013
2012-Fig 5. SR, Pg 11
Chlamydia—Prevalence Among Persons Aged 14–39 Years by
Sex, Race/Ethnicity, or Age Group, National Health and Nutrition
Examination Survey, 2005–2008
NOTE: Error bars indicate 95% confidence intervals.
2012-Fig 10. SR, Pg 13
Chlamydia—Rates by Sex, United States
1992–2013
NOTE: As of January 2000, all 50 states and the District of Columbia have regulations that require the reporting of chlamydia
cases.
2012-Fig 1. SR, Pg 9
Chlamydia screening reduces complications
Reported cases of Chlamydia trachomatis
San Francisco women, 1993–2004
Reported pelvic inflammatory disease cases
San Francisco County, 1993–2004
Ectopic pregnancies
San Francisco General Hospital 1993–2004
Moss N J et al. J Infect Dis. 2006;193:1336-1338
Fig. 1
Nucleic Acid Amplification Tests in the Diagnosis of Chlamydial and Gonococcal
Infections of the Oropharynx and Rectum in Men Who Have Sex With Men.
SCHACHTER, JULIUS; MONCADA, JEANNE; LISKA, SALLY; SHAYEVICH, CLARA; KLAUSNER, JEFFREY
Sexually Transmitted Diseases. 35(7):637-642, July 2008.
Prevalence of chlamydial and gonococcal infection in
symptomatic versus asymptomatic men who have sex
with men by anatomical site.
2
© Copyright 2008 American Sexually Transmitted Diseases Association. Published by Lippincott Williams & Wilkins, Inc.
Options for specimen collection
1) Cervical swab
2) Vaginal swab
3) Self-collected vaginal swab
4) Urine
5) Rectal swab
6) Self-collected rectal swab
Rectal Chlamydia Positivity, San Francisco
(n=6,861)
15%
10%
9.8%
Mean positivity 8.4% (n=576+)
7.4%
8.3%
7.1%
5.2%
11.3%
8.1%
6.2%
4.7%
5%
Private MD
Homeless/TG
Clinic
Sex Wrk Clinic
2 HIV Clinics
HIV
Seroconverters
HIV Testing Prg
Community
Screening
MSM Clinic
STD Clinic
0%
29
86%
Most rectal chlamydial infections in gay/bisexual
men are asymptomatic, San Francisco
14%
Asymptomatic
Symptomatic
86%
Rectal chlamydia
n=316
30
Kent et al. Clin Inf Dis, 2005
Prior rectal infections increase HIV risk
Bernstein KT et al, JAIDS, 2010
STI positivity in high-risk MSM
N = 6659 HIV negative
N = 205 newly
diagnosed HIV-infected
32
Scott KC et al. JAIDS 2008
HIV and STI incidence among MSM/TW, Lima, Peru 2009-2012
WHO Guidance on
STIs in MSM/TW
Treatment for uncomplicated
chlamydial infection
1)
2)
3)
4)
Azithromycin 1 gm orally once
Doxycycline 100 mg orally twice daily for 7 days
Amoxicillin 500 mg po tid x 7 days
Levofloxacin 500 mg po qd x 7 days
•
Partner treatment
– SB 648, CA Law January 2001
•
Re-testing at 3 months
Treatment for uncomplicated
chlamydial infection
1)
2)
3)
4)
Azithromycin 1 gm orally once
Doxycycline 100 mg orally twice daily for 7 days*
Amoxicillin 500 mg po tid x 7 days
Levofloxacin 500 mg po qd x 7 days
*Preferred in rectal infection
Case
44 year old man with new
lesion near his anus
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Differential diagnosis of anogenital ulcer
Sexually transmitted diseases
Other
• Primary syphilis
• Genital herpes
• Chancroid
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Fixed drug reactions
Skin flora infections
Autoimmune conditions
Trauma
Insect bite
1000x darkfield microscopy
Treponema pallidum pallidum, bacterial spirochete
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Primary syphilis – penile chancres
Secondary syphilis: trunk rash
Secondary syphilis: palmar and plantar lesions
Secondary syphilis: split papules, “moth-eaten” alopecia,
mucous patches, and condyloma lata
J. Engelman
Split papule (mucous patch)
www.merckmedicus.com
Moth-eaten alopecia
J. Engelman
Mucous patch
Katz
Mucous patch
Katz
Condyloma lata
Latent syphilis
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Syphilis—Reported Cases by Stage of
Infection, United States, 1941–2013
Primary and Secondary Syphilis —
Reported Cases by Sex and Sexual Behavior,
33 areas*, 2007–2013
2012-Fig 29. SR, Pg 32
Primary and Secondary Syphilis—Rates by
Age and Sex, United States, 2013
2012-Fig 35. SR, Pg 35
Primary and Secondary Syphilis—Rates by
Race/Ethnicity, United States, 2009–2013
* AI/AN = American Indians/Alaska Natives; NHOPI = Native Hawaiian and Other Pacific Islanders.
NOTE: Includes 38 states and the District of Columbia reporting race/ethnicity data in Office of Management and
Budget compliant formats during 2008-2012.
2012-Fig 38. SR, Pg 36
Increases in STDs in MSM
Increases in early
syphilis in MSM in
Sydney; London,
Amsterdam,
Oslo…
Primary and Secondary Syphilis — United States
Reported Cases by Sex and Sexual Behavior, 33 areas*
2007–2013
STD increases related to increases in sexual risk behavior
and in the U.S. decreases in the public health response
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Primary & Secondary
and Latent < 1 year syphilis treatment
HIV (-)/(+)
2.4 million units of benzathine penicillin G-LA
Pregnant
2.4 million units of benzathine penicillin G-LA
PCN-allergic:
HIV(-)/(+)
doxycycline 100 mg po bid x 14 d
Pregnant
desensitize, then benzathine penicillin G-LA
• Prophylactic treatment: All contacts to syphilis within past 90
days should be treated regardless of serologic test result with
benzathine penicillin G 2.4 MU IM once
CDC STD Treatment Guidelines, 2015
All those syphilis tests
• Non-treponemal tests (RPR, VDRL)
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–
–
–
Detects antibody to cardiolipin-lecithin-phospholipids
Rise and fall with infection and treatment over time
4-fold change in titer (1:2 to 1:8 or 1:64 to 1:16) is significant
Specificity = 98% (false-positives in IDU, auto-immune, etc)
• Treponemal tests (FTA-Abs, TPPA, TP EIA, rapid TP)
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–
–
–
Detects antibody to Treponemal antigen
More sensitive and develop earlier
Stay positive for “life” (85%)
Indicate past or current infection
50
Klausner, Current STD Diagnosis and Management 2007
Syphilis and HIV infection
• Multiple chancres
• May present with overlapping primary and secondary
manifestations
• Rarely abnormal serology but slower decline
• Increased risk neurosyphilis
Zetola and Klausner, Clin Inf Dis 2007.
AIDS, 2004
San Francisco, 2009
San Francisco, early 2000s
Texas
August 20, 2003
The Daily Show Sore Loser
Syphilis treatment challenges
• Lack of well-studied alternatives to
penicillin G benzathine
• HIV-infection
• Azithromycin/macrolide resistance
• Neurosyphilis
• Follow-up
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Reproductive Rate (R0)
• R0 = β x c x d
Where β = transmission efficiency
c = contact rate
d = duration of infectiousness
STD control measures
• Individual level
– Reduce exposure
– Reduce infection
– Reduce sequelae of infection
• Population level
– Reduce transmission, ↓ R0
STD chemoprophylaxis
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Bolan R et al. STD, 2015
Sources for more STD information
•
Me
– JDKlausner@mednet.ucla.edu
– AskDrK.org
• CDC
– www.cdc.gov/std
•
Current STD management textbook
Thank you